The major objectives of this research are: (l) to understand the genesis of basal tone in the lower esophageal sphincter (LES); (2) to identify the nature of the inhibitory neurotransmitter that causes relaxation of the LES upon swallowing; and (3) to understand the mechanism of peristalsis and its abnormalities in the esophageal body. These studies will be performed in anesthetized opossums. Cats and dogs will be used in certain experiments to identify any species variations. Basal sphincter tone will be studied in isolated dispersed smooth muscle cells from the lower esophageal sphincter. Electromyographic recordings of the LES and study of transmembrane potential in single cells will help define electrogenic basis of basal tone. Histological studies will be done to define the density of neurons and the types of intramural neurons in the LES. The nature of inhibitory transmitter will be evaluated by pharmacologic studies, by investigation of the nature of the inhibitory substance that is related in the venous drainage of the LES during vagally stimulated sphincter relaxation and by immunohistochemical studies on the intramural neurons. The mechanism of peristalsis will be investigated by recording electrical activity in the vagal efferents. Electrical activity and intraluminal pressures will be recorded for the esophageal body and influence of different manipulation on latencies of response and speed and orientation of peristalsis will be investigated.